Postponing Early intrauterine Transfusion with Intravenous immunoglobulin Treatment; the PETIT study on severe hemolytic disease of the fetus and newborn


      Intrauterine transfusion for severe alloimmunization in pregnancy performed <20 weeks’ gestation is associated with a higher fetal death rate. Intravenous immunoglobulins may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions.


      We evaluated whether maternal treatment with intravenous immunoglobulins defers the development of severe fetal anemia and its consequences in a retrospective cohort to which 12 fetal therapy centers contributed.

      Study Design

      We included consecutive pregnancies of alloimmunized women with a history of severe hemolytic disease and by propensity analysis compared index pregnancies treated with intravenous immunoglobulins (n = 24) with pregnancies managed without intravenous immunoglobulins (n = 28).


      In index pregnancies with intravenous immunoglobulin treatment, fetal anemia developed on average 15 days later compared to previous pregnancies (8% less often <20 weeks’ gestation). In pregnancies without intravenous immunoglobulin treatment anemia developed 9 days earlier compared to previous pregnancies (10% more <20 weeks), an adjusted 4-day between-group difference in favor of the immunoglobulin group (95% confidence interval, –10 to +18; P = .564). In the subcohort in which immunoglobulin treatment was started <13 weeks, anemia developed 25 days later and 31% less <20 weeks’ gestation (54% compared to 23%) than in the previous pregnancy. Fetal hydrops occurred in 4% of immunoglobulin-treated pregnancies and in 24% of those without intravenous immunoglobulin treatment (odds ratio, 0.03; 95% confidence interval, 0–0.5; P = .011). Exchange transfusions were given to 9% of neonates born from pregnancies with and in 37% without immunoglobulin treatment (odds ratio, 0.1; 95% confidence interval, 0–0.5; P = .009).


      Intravenous immunoglobulin treatment in mothers pregnant with a fetus at risk for hemolytic disease seems to have a potential clinically relevant, beneficial effect on the course and severity of the disease. Confirmation in a multicenter randomized trial is needed.

      Key words

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      Linked Article

      • Revisiting the use of intravenous immune globulin (IVIG) for Kell alloimmunization
        American Journal of Obstetrics & GynecologyVol. 219Issue 3
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          The development of anti-D (Rh) immune globulin and its antepartum and postpartum use is one of the remarkable success stories in obstetrics as it has nearly eliminated fetal deaths from Rh immunization. In contrast, Kell immunization, although rare, is still present since there is no prophylactic anti-Kell immune globulin. The critical titer for identifying affected pregnancies and optimal care of Kell-sensitized pregnancies has remained controversial.1,2 When severe Kell alloimmunization occurs, intrauterine blood transfusion is essential to prevent fetal death.
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